The overall objective of this research is to gain better understanding of cellular regulatory mechanisms involved in representative members of parasitic helminths belonging to the class Trematoda. We intend to study the biochemical nature of the serotonin-activitated adenylate cyclase and other allied enzymes involved in the regulation of cyclic AMP levels in the cell. The liver fluke Fasciola hepatica will be used as a model organism with some comparative studies on Schistosoma mansoni. Binding properties of serotonin receptors to different analogs will be investigated. An attempt will be made to solubilize the serotonin receptors and to study their biochemical and physical properties. Other components of adenylate cyclase in the plasma membrane will be investigated. These include the GTP and the catalytic components. Isolation of these components will be carried out and an attempt will be made to reconstitute the regulatory enzyme complex. Studies on the nature of cAMP-dependent protein kinase, localization of the enzyme within the cell and identification of the natural protein substrates that are phosphorylated by the enzyme will be undertaken. Studies will be conducted to identify the relationship between these phosphorylated proteins and the effects of serotonin on metabolism and motility. cAMP phosphodiesterase from the liver fluke will be purified and its properties will be characterized. Regulatory mechanisms involved in control of phosphodiesterase will be studied and the relationship between the effect of methyl xanthine derivatives on the enzyme and on the parasite motility will be tested. We also plan to identify serotonin or other indoleamines naturally present in the parasites and to localize their sites in the liver fluke, F. hepatica. Regulatory mechanisms involved in the synthesis, binding and release of serotonin or other indoleamines will be investigated. One essential theme that runs through our research is identification of the differences as well as the similarities of properties of these enzyme systems in parasite and host. Our basic aim is to identify sites in the parasite that are amenable for pharmacologic manipulation without affecting the host.